1. Field of Invention
The present invention is principally concerned with the use of sulfamic acid derivatives in the treatment of mammals in several therapeutic areas. More particularly the invention is concerned with the pharmaceutical use of compounds and pharmaceutical compositions therefor which compounds carry one or more aminosulfonyloxy radicals or substituted aminosulfonyloxy radicals, especially sulfamate esters prepared from compounds having one or more hydroxyl groups, most notably in the treatment of chronic arthritis and osteoporosis. Certain of the compounds are novel and a certain process for preparing the compounds is also novel.
2. Information Disclosure Statement
Numerous references disclose sulfamate esters derived from a phenol or naphthol. Wegler, U.S. Pat. No. 2,839,562, discloses insecticide sulfamate esters of the formula ArOSO.sub.2 NRR.sup.1 where Ar is naphthyl, phenyl or phenyl substituted by chlorine, methyl or nitro, and R and R.sup.1 are selected from alkyl, cycloalkyl, aryl or form a heterocyclic group with the interposed nitrogen. Dunbar, U.S. Pat. No. 3,082,238, discloses sulfamate esters of the formula Ar(OSO.sub.2 NR.sub.2).sub.1-2 where Ar is naphthyl, phenyl or phenyl substituted by chlorine, methyl, ethyl, nitro, diloweralkylamino, diloweralkylaminoalkyl, or phenyl and R is loweralkyl useful as a herbicide or fungicide. The French Patent 1,555,976 discloses a phenylsulfamate ester of the formula: ##STR1## where X is H, OH, methyl, chlorine, bromine, methoxy, methanesulfonyl, methoxycarbonyl or phenyl.
Other references disclosing sulfamate esters derived from phenol, substituted phenol, or other hydroxyaryl compounds are Hedayatullah and Guy, Synthesis (1978), p. 357; G. Lohause, Chem. Ber. 105, 2791-99 (1972); Dubois, J. Org. Chem. 45, 5373-75 (1980) and Spillane, J. Chem. Soc., Perkin. Trans. I, 3, 677-9 (1982). Maryanoff, in U.S. Pat. No. 4,513,006 discloses anticonvulsant sulfamate esters of cyclohexylmethanol, 1,2,3,4-tetrahydronaphthalene-2-methanol, or tetrahydropyranyl-2-methanol monosulfamate derivatives of the formula ##STR2## where R.sup.2 and R.sup.3 and/or R.sup.4 and R.sup.5 may form a substituted methylenedioxy group. These monosaccharide derivatives are also disclosed to be useful as carbonic anhydrase inhibitors. In U.S. Pat. No. 4,591,601 Maryanoff discloses the sulfamate ester of 2-substituted-4-(1,3-dioxolane) methanols useful as anticonvulsants. Other sulfamate esters of various furanose and pyranose monosaccharide derivatives, cycloalkylmethanol, bi (and tri) cycloalkylmethanol, 2-phenylethanol, 2,2-diphenylethanol, and 4,5-benzoisoxazol-3-methanol are disclosed in J. Med. Chem. 30, 880-887 (1987). Usov. Izv. Akad. Nauk. SSSR. Ser. Khim. 1975 (1084-8), CA 83:131847t, reports mass spectral studies of monosulfamate esters of acetylated monosaccharides. Shuman et al. in J. Amer. Chem. Soc. 91, 3391-2 (1969) describes a sulfamate ester of a fluorinated nucleoside.
N-benzylsulfamate esters of cyclohexanol and n-hexanol are described by Spillane and Burke, Synthesis, 1021-1024 (1986). The German Patent 2,559,210 discloses contraceptive utility for glycol sulfamate esters of the formula R.sup.2 R.sup.3 NSO.sub.2 OCH.sub.2 (CRR.sup.1).sub.n CH.sub.2 OSO.sub.2 NR.sup.2 R.sup.3 where R.sup.2 and R.sup.3 are H, alkyl, aryl or R.sup.2 NR.sup.3 is pyrrolidine or piperidine; R and R.sup.1 are H, alkyl, arylalkyl and n is 0-8. Erucyl sulfamate and oleyl sulfamate are disclosed as slip additives for polyethylene in U.S. Pat. No. 3,661,830. Weiss and Schulze, Liebigs Ann. Chem. 729, 40-51 (1969) disclose the synthesis of sulfamate esters of the formula R.sup.1 OCH.sub.2 CH.sub.2 OSO.sub.2 NHR where R.sup.1 is loweralkyl or unsubstituted phenyl and R is loweralkyl.
2-(Substitutedphenyl)ethanol esters of sulfamic acid useful in treating convulsions and glaucoma are disclosed by Maryanoff in U.S. Pat. No. 4,792,569.
Markley, U.S. Pat. No. 4,824,475 discloses herbicidal activity of sulfamate esters of the formula: ##STR3## where R.sup.2 and R.sup.3 are phenyl, loweralkylphenyl, naphthyl, or benzyl and T is H, acetyl, propionyl, or trifluoroacetyl.
Gates and Baldwin, U.S. Pat. No. 4,222,767, disclose herbicidal sulfonates and sulfamates of the formula: ##STR4## where R.sup.9 can be a C.sub.1 -C.sub.4 loweralkyl (or dialkyl)amino group, X is --CHR.sup.3 OR.sup.4 and Y is --OR.sup.5. Among the definitions for the R.sup.4 and R.sup.5 groups are --SO.sub.2 R.sup.11 where R.sup.11 can be C.sub.1 -C.sub.6 alkyl (or dialkyl)amino. Thus this disclosure encompasses phenyl sulfamate esters and 1,3' (and 6') phenylalkyl sulfamate esters.
An intermediate for azo dye preparation disclosed in German Offen. 2,531,445 has the formula PhNEtCH.sub.2 CH.sub.2 OSO.sub.2 NMe.sub.2. Compounds having the formula: ##STR5## wherein R.sup.3 and R.sup.4 are hydrogen or loweralkyl and R.sup.2 is loweralkyl are disclosed in German Offen. 2,417,764 (CA 84:30709q) as herbicides.
The prior art thus discloses sulfamate esters of phenol, substituted phenol, naphthol, monosaccharides, heterocyclic methanols, pbhenoxyethanol, loweralkoxyethanols, and phenylethanol. No disclosure has been found for alkyl groups substituted by 2-sulfamate groups and further substituted by aryloxy, arylcarbonyl aryloxycarbonyl, or heteroaryl group nor alkyl groups having more than 2 sulfamate ester groups.
Although some of the compounds of the methods of this invention fall within the disclosures of the above references, none of the above references disclose the uses of sulfamate esters in the treatment of chronic arthritis or treating or preventing osteoporosis. Certain compounds of this invention resemble those disclosed in the above references but are not encompassed by the formulas disclosed above and are believed to be novel.